Understanding the evolutionary selective forces that fashioned the sex chromosomes from a putative ancestral autosome pair is a major problem in biology (reviewed in Khil and Camerini-Otero (2005) Crit. Rev. Biochem. Mol. Biol. 40, 313). A few years ago it was reported that genome-wide analyses of C. elegans and D. melanogaster revealed that male-specific genes are underrepresented on the X-chromosome whereas the opposite was reported for about 2 dozen mouse spermatogonial genes. Is the mouse really different? Our analysis of the Spo11 adult mice microarray data provided a time line for the expression of testis genes. We found that those genes expressed in cells late in meiosis, including the majority of testis-enriched genes, are underrepresented on the X. However, early genes are overrepresented. Since the previously published mouse data pertained to early spermatogonial genes only, these results reconcile all the data. Furthermore, we added a missing piece of the puzzle by proposing that the demasculinization (removal of male genes) of the X chromosome in most organisms is influenced by inactivation of the sex chromosomes during male meiosis (Khil et al. (2004) Nat. Genet. 36, 642 and commentary in Reinke (2004) Nat. Genet. 36, 548). One manner by which this reshaping of the X chromosome is achieved is by retrotransposition from the X chromosome to autosomes much more frequently than between autosomes (Shiao et al.(2007) Mol Biol Evol). Recently we have worked on three separate areas within this general area. First, we have been investigating how a structure we have named the Pseudo Sex-Body (PSB) is formed. The PSB is observed in the absence of double-strand breaks in a Spo11 knockout mouse as an accumulation of gammaH2AX, akin to the accumulation seen on the X and Y chromosomes in the normal sex body seen in wild-type mice. As we have previously shown that the PSB does not include the sex chromosomes (X and Y: Bellani et al. (2005) J Cell Science 118, 3233) we have been investigating by using ChIP-Seq whether particular chromosomes or genomic regions are encased or decorated by gammaH2AX in the PSB. This is still an ongoing project. Second, in collaboration with Satoshi Namekawa at Cincinnati Children's Hospital we have shown that MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells (Ichijama et al. (2011) Genes and Development 25, 959). Finally, in collaboration with James Turner at National Institute for Medical Research at Mill Hill, London we have identified Rsx, an RNA that coats the inactive female marsupial X chromosome (Grant et al. (2012) Nature 487, 254). This has been a long-standing biological mystery as it has been known that marsupial females inactivate only the paternally-inherited X chromosome, not as in mice and man where either the paternal or maternal chromosome is inactivated. For this reason, it has been proposed that the mechanism of X chromosome inactivation in marsupials does not involve an RNA that coats the inactive chromosome, as is the case for Xist RNA in eutherian mammals such as mice and man. In this work, such an RNA has been identified even though it bears no sequence homology to Xist. No significant progress to report this year, although the collaboration on Rsx is ongoing.